Asymmetric dihydroxylation of trans-cinnamates under high-pressure conditions: Substantial increase of turnover number

Article abstract of DOI:10.1016/S0957-4166(01)00296-8

Under high-pressure conditions, a substantial increase in the turnover number was observed in the osmium-catalyzed asymmetric dihydroxylation of trans-cinnamate derivatives.

Full text of DOI:10.1016/S0957-4166(01)00296-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1533–1535
Asymmetric dihydroxylation of trans-cinnamates under
high-pressure conditions: substantial increase of turnover number
Choong Eui Song,a,* Chun Rim Oh,a Eun Joo Roha and Jung Hoon Choib,*
aLife Sciences Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, South Korea
bDepartment of Chemistry, Hanyang University, Seoul 133-791, South Korea
Received 31 January 2001; accepted 25 June 2001
Abstract—Under high-pressure conditions, a substantial increase in the turnover number was observed in the osmium-catalyzed
asymmetric dihydroxylation of trans-cinnamate derivatives. © 2001 Elsevier Science Ltd. All rights reserved.
The osmium-catalyzed asymmetric dihydroxylation
(AD) of alkenes using cinchona alkaloid derivatives
as chiral ligands is one of the most popular syn-
thetic methods that has been devised and contin-
uously improved by Sharpless et al.1 In particular,
the catalytic systems based on bis-cinchona alkaloids,
enantioselectivity, we carried out AD reaction of trans-
cinnamates 1a–c under homogeneous conditions8,9
using N-methylmorpholine N-oxide (NMO) as a co-
oxidant in acetone–H2O (10:1). The AD products of
1a–c have already been successfully used as key inter-
mediates for some pharmacologically active com-
pounds, such as the side-chain of Paclitaxel,10
Diltiazem11 and Chloramphenicol.12 As shown in Table
1, experiments carried out under high pressure (entries
2, 5, 6, 8, 10, 12 and 14) clearly showed that the lifetime
of the catalyst was dramatically prolonged. Experi-
ments with 0.01 mol% of osmium catalyst under nor-
mal pressure (entries 3, 4, 9 and 13) revealed that the
maximum TON for the osmium catalyst is 1900 (19%
yield, entry 4). However, under high pressure (10 kbar,
entries 5, 6, 10 and 14), the TONs increased up to 7800
(entry 10). To the best of our knowledge, this is the
highest TON value ever reported in osmium-catalyzed
AD. The observed increase in turnover number under
high-pressure conditions could be attributed to the
stabilization of catalyst by strongly enforcing coordina-
tion of chiral ligand to osmium. However, the enan-
tioselectivity was decreased under 10 kbar, which might
be ascribed to a too compact conformation of Os-com-
plex, in which the substrates cannot fit in binding clefts
well.13 On the other hand, experiments carried out
under 20 bar using 0.05 mol% of osmium catalyst gave
useful results. Under 20 bar, the AD reaction proceeded
still much faster than under normal pressure, and e.e.
was retained (compare the results of entries 2, 8 and 12
with those of entries 1, 7 and 11).
such
as
1,4-bis(9-O-dihydroquininyl)phthalazine
((DHQ)2PHAL) and 1,4-bis(9-O-dihydroquinidinyl)-
phthalazine ((DHQD)2PHAL), have received a great
deal of interest, due to their broad scope of substrates,
high enantioselectivities2 and substantial rate-accelera-
tion effect.3 Enzyme-like non-covalent binding in a
binding pocket of this type of ligands seems to be the
cause of the substantial rate accelerations and the abil-
ity to deliver high enantioselectivities.3b,4 However, the
relatively low turnover numbers of this quite expensive
catalytic system has limited large-scale applications.
Very recently, Reiser et al. have reported that the
volume of activation for the osmium-catalyzed non-AD
of ethyl trans-cinnamate was determined to be −12 2
cm3 mol−1,5 i.e. it can be expected that the reaction rate
could be increased under high-pressure conditions.6
This result intrigued us and led us to examine the effect
of high pressure on the reaction rate and enantioselec-
tivity in the catalytic AD reaction. Herein, we report
our preliminary results on the influence of high pres-
sures on the osmium-catalyzed AD of trans-cinna-
mates, which revealed a substantial increase of the
turnover number (TON) of the catalyst.7
To examine the high-pressure effect on osmium-cata-
lyzed AD of alkenes, in terms of reactivity as well as
In conclusion, we have demonstrated that high pressure
might be used in the catalytic AD reaction of trans-cin-
* Corresponding authors.
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00296-8

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C. E. Song et al. / Tetrahedron: Asymmetry 12 (2001) 1533–1535
Table 1. Asymmetric dihydroxylation of trans-cinnamate derivatives
OsO4 (0.01 mol%)
(DHQ)2PHAL (1.25 mol%)
NMO
OH
O
O
OR2
OR2
acetone-H2O(10:1), 10oC
a : R1 = H, R2 = CH3
b : R1 = OCH3, R2 = CH(CH3)2
c : R1 = NO2, R2 = CH(CH3)2
OH
2a-2c
R1
R1
1a-1c
Entrya
Substrate
OsO4 (mol%)
Pressure (bar)
Time (h)
Yieldb (%)
TONc
% E.e.d
Config.e
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1c
1c
1c
1c
0.05
0.05
0.01
0.01
0.01
0.01
0.05
0.05
0.01
0.01
0.05
0.05
0.01
0.01
1
20
1
48
48
24
168
24
168
48
34
72
13
19
26
44
73
82
12
78
67
89
12
75
680
1440
1300
1900
2600
4400
1460
1640
1200
7800
1340
1780
1200
7500
96.2
96.1
94.1
94.1
85.5
85.0
97.0
97.3
96.1
91.1
95.5
96.0
95.8
81.2
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
1
104
104
1
20
1
48
9
168
168
48
48
168
168
10
11
12
13
14
104
1
20
1
104
a All reactions were carried out on a 1 mmol scale using 1.25 mol% of (DHQ)2PHAL.
b Isolated yields by column chromatography.
c Turnover number.
d % E.e.s of products were determined by chiral HPLC analysis.
e Absolute configurations were determined by comparison of physical data with those of authentic compounds.
namates as a tool to increase the turnover number of
the catalyst. Further investigations to explore the
effects of high pressure in asymmetric catalysis are
currently under way.
tion of methyl trans-cinnamate 1a (162.2 mg, 1.0 mmol)
in acetone–water (10 mL). Then the autoclave was
closed, pressurized with nitrogen, and stirred. After 48
h, the reaction mixture was worked-up as described
above to yield 141.3 mg (72%) of the diol 2a (96.1%
e.e.).
Representative procedure of AD reactions under high-
pressure conditions (10 kbar):
A
solution of
The e.e.s of products 2a–c were determined by chiral
HPLC. For 2a: Chiralcel OJ, iso-PrOH/hexane (1/4),
1.0 mL min−1; 11.7 min (2R,3S), 17.6 min (2S,3R). For
2b: Chiralpak AD, iso-PrOH/hexane (15/85), 1.0 mL
min−1; 17.8 min (2S,3R), 20.3 min (2R,3S). For 2c:
Chiralpak AD, iso-PrOH/hexane (1/4), 1 mL min−1;
14.9 min (2S,3R), 21.5 min (2R,3S).
(DHQ)2PHAL (9.7 mg, 0.0125 mmol), NMO (175.7
mg, 1.5 mmol) and aqueous solution of OsO4 (7 mL,
0.155 mmol/L, 0.1 mmol) in acetone–water (10/1, v/v, 3
mL) was transferred by syringe into a Teflon capsule. A
solution of iso-propyl trans-4-methoxycinnamate 1b
(220.3 mg, 1.0 mmol) in acetone–water (2 mL) was
added to the mixture by means of syringe and cooled to
−78°C before the AD reaction to prevent any further
reaction. After the Teflon cell was sealed, it was placed
in an autoclave, where the AD reaction was performed
without stirring at 10°C under pressure (10 kbar). After
168 h, the reaction was quenched with Na2SO3 solu-
tion. The organic material was extracted three times
with ethyl acetate, and the combined extracts were
dried with Na2SO4. After evaporation of the solvent,
the crude product was purified by chromatography on
silica gel to give the diol 2b (198.3 mg, 78%). E.e.=
91.1%.
Acknowledgements
This research was supported by a grant from the Min-
istry of Science and Technology in Korea.
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84% e.e. (10°C), 90% e.e. (20°C), 92% e.e. (30°C) and
93% e.e. (40°C); cf. 1 bar: 96% e.e. (10°C), 94% e.e.
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.